Definium Receives Second FDA Breakthrough Therapy Designation for DT120 (Lysergide) ODT in Major Depressive Disorder

Definium Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to DT120 (lysergide) orally disintegrating tablet (ODT) for the treatment of major depressive disorder (MDD). The designation follows positive results from the Phase 3 Emerge study, in which a single 100 µg dose of DT120 ODT demonstrated an 8.1-point placebo-adjusted improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6 (p<0.0001), with reported efficacy sustained through Week 12.

The designation represents the second FDA Breakthrough Therapy designation for the DT120 development program, following its earlier designation for generalized anxiety disorder (GAD).

FDA Breakthrough Therapy Designation Supported by Phase 3 Data

The FDA’s Breakthrough Therapy designation is a process designed to expedite the development and review of therapies intended to treat serious conditions where preliminary clinical evidence indicates that the therapy may demonstrate substantial improvement over available therapy on one or more clinically significant endpoints.

For DT120, the MDD designation was supported by findings from the Phase 3 Emerge study demonstrating a statistically significant improvement in depressive symptoms following a single dose.

Rob Barrow, Chief Executive Officer of Definium Therapeutics, said the second Breakthrough Therapy designation, following the Phase 3 Emerge results ((NCT06941844)), underscores the potential of DT120 to address serious mental health disorders and supports continued development across MDD and GAD.

Phase 3 Emerge Study Demonstrates Durable MADRS Improvement

In the Phase 3 Emerge study, a single 100 µg dose of DT120 ODT produced an 8.1-point placebo-adjusted improvement in MADRS total score at Week 6, with statistical significance at p<0.0001.

The reported efficacy was sustained through Week 12 following the single dose, indicating a durable treatment response over the assessment period.

The findings provide the clinical basis for the FDA’s Breakthrough Therapy designation in MDD and represent an important development milestone for the DT120 program.

MDD Remains a Significant Unmet Medical Need

MDD is a serious mental health disorder and a leading cause of disability worldwide. The company cites more than 21 million U.S. adults experiencing a major depressive episode each year.

MDD can involve persistent symptoms including feelings of worthlessness, fatigue, impaired social functioning, and recurrent thoughts of death. Despite the availability of first-line treatments, fewer than one-third of patients achieve remission, highlighting the need for additional treatment options.

The company also identifies delayed onset of clinical activity, poor tolerability, and frequent treatment switching, augmentation, and discontinuation as continuing challenges in the MDD treatment paradigm.

DT120 ODT Formulation and Mechanism

DT120 ODT is Definium’s proprietary and pharmaceutically optimized formulation of lysergide, an ergoline derivative belonging to the group of classic serotonergic psychedelics. It acts as a partial agonist at serotonin 2A (5-HT2A) receptors.

DT120 ODT is the tartrate salt form of lysergide and incorporates Catalent’s Zydis® fast-dissolve ODT technology. The formulation is designed to provide several potential advantages, including faster absorption and onset of transient cognitive, perceptual, and affective changes, improved bioavailability, and a lower incidence of gastrointestinal side effects.

Lysergide, also known as LSD, is a classic psychedelic that temporarily alters perception, cognition, and emotion. Its acute perceptual, cognitive, and affective effects are mediated by agonism of the serotonin 5-HT2A receptor, while mechanistic hypotheses in psychiatric research have suggested that lysergide may produce sustained increases in neuroplasticity in various brain regions.

DT120 Development Program

Definium is developing DT120 ODT for multiple serious brain health disorders, including MDD, GAD, and posttraumatic stress disorder (PTSD). The company is also exploring potential applications in other serious brain health disorders.

The DT120 development program has now received FDA Breakthrough Therapy designation for both GAD and MDD, underscoring the program’s development across multiple psychiatric indications.

Definium also maintains a multi-layered intellectual property strategy intended to protect and extend the long-term value of the DT120 ODT franchise, including patents covering composition, formulation, and methods of use.

Reference

Definium Therapeutics Receives Breakthrough Therapy Designation for DT120 (lysergide) Orally Disintegrating Tablet (ODT) in Major Depressive Disorder (MDD) Following Positive Phase 3 Results, Definium Therapeutics, 08 September 2026